High glucose diet induces hepatic iron overload contributing to metabolic dysfunction

Area of Science:

• Biochemistry
• Metabolic disorders
• Iron metabolism

Background:

• Iron is vital for cellular functions, and its imbalance (dyshomeostasis) is linked to hyperglycemia and metabolic disorders.
• The precise mechanisms connecting iron dyshomeostasis and hyperglycemia remain unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the mechanisms linking glucose metabolism and iron homeostasis.
• To explore the therapeutic potential of targeting iron dyshomeostasis in metabolic dysfunction.

Main Methods:

• A 4-week study using mice with glucose-supplemented water to induce metabolic shifts.
• Analysis of liver and serum iron markers and iron speciation using liquid chromatography with inductively-coupled plasma mass spectrometry (LC-ICP-MS).
• Development of cell-based models to replicate hyperglycemia-induced iron dyshomeostasis.

Main Results:

• Glucose supplementation altered iron regulation, increasing transferrin-bound iron uptake and causing liver iron overload, despite consistent dietary iron intake.
• Metformin treatment normalized iron regulation in the cell models.
• Deferoxamine, an iron chelator, restored normal glucose metabolism.

Conclusions:

• Early hyperglycemia disrupts iron homeostasis, leading to iron overload.
• Targeting iron overload presents a potential therapeutic strategy for metabolic dysfunction.
• Metformin and deferoxamine demonstrate efficacy in restoring iron and glucose balance, respectively.